The goal of our research is to examine the immunomodulatory and anti- inflammatory properties of lactoferrin in order to evaluate the potential use of this protein in the treatment and/or prevention of pulmonary inflammatory diseases such as asthma. Recently we demonstrated a novel mechanism of anti-inflammatory action by lactoferrin whereby this protein inhibited allergen induced cutaneous inflammation that is mediated by de novo synthesis of tumor necrosis factor alpha. This exciting finding, together with the established anti-inflammatory functions and presence of this protein in bronchial secretions suggest that lactoferrin may be of therapeutic use in alleviating allergen induced inflammatory diseases such as asthma. To further substantiate this hypothesis, we will (1) use lactoferrin knock-out mice to study the physiological significance of lactoferrin ablation in pulmonary disease and (2) use aerosolized, biologically active recombinant lactoferrin to examine the preventative and/or therapeutic use of this protein in an established murine model of asthma. These studies will provide important proof of principal that the anti-inflammatory activities of lactoferrin may provide a novel alternative anti-inflammatory treatment for pulmonary disease, including asthma. PROPOSED COMMERCIAL APPLICATIONS: Recent increases in the incidence and severity of asthma have prompted an intense search for novel agents to treat this chronic inflammatory disease. While corticosteroids are the accepted treatment of asthmatic patients, potential adverse side effects limit their usefulness. We demonstrated a novel anti-inflammatory role of LF; this protein can inhibit the action of tumor necrosis factor alpha. The studies outlined here will form the foundation to establish the potential commercial anti-inflammatory applications of LF including: l) use of LF aerosols as a novel anti-inflammatory preventative therapy for patients at high risk for asthma; 2) use of LF aerosols as novel therapeutic agents to treat chronic inflammation associated with asthma.